Trial Outcomes & Findings for A Clinical Trial of PRAX-944 in Participants With Essential Tremor (NCT NCT05021978)

NCT ID: NCT05021978

Last Updated: 2024-03-01

Results Overview

The TETRAS upper limb score is calculated as the sum of the 6 separate upper-limb maneuvers assessed by the clinician: forward-outstretched postural tremor \[right\], forward outstretched postural tremor \[left\], lateral wing-beating postural tremor \[right\], lateral wing-beating postural tremor \[left\], kinetic tremor \[right\], kinetic tremor \[left\], each on a 0 (no tremor) to 4 (maximum tremor) severity scale in 0.5-point increments. TETRAS Part 4 score for both upper limbs ranged from 0 to 24, higher scores indicated more severe tremor. A negative change from baseline indicated less tremor. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Baseline (Day 0), Days 7 and 14

Results posted on

2024-03-01

Participant Flow

Participant milestones

Participant milestones
Measure	Part A: PRAX-944 20mg to 40mg Open-Label Titration (OLT) Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 20mg to 120mg OLT Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks.	Part B: PRAX-944 120mg Randomized Withdrawal Phase (RWD) Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
PART A OLT Phase (Day 1 to Day 21) STARTED	7	0	0	0
PART A OLT Phase (Day 1 to Day 21) COMPLETED	6	0	0	0
PART A OLT Phase (Day 1 to Day 21) NOT COMPLETED	1	0	0	0
PART B OLT Phase (Day 1 to Day 42) STARTED	0	17	0	0
PART B OLT Phase (Day 1 to Day 42) COMPLETED	0	11	0	0
PART B OLT Phase (Day 1 to Day 42) NOT COMPLETED	0	6	0	0
PART B RWD Phase (Day 43 to Day 70) STARTED	0	0	6	5
PART B RWD Phase (Day 43 to Day 70) COMPLETED	0	0	6	5
PART B RWD Phase (Day 43 to Day 70) NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: PRAX-944 20mg to 40mg Open-Label Titration (OLT) Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 20mg to 120mg OLT Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks.	Part B: PRAX-944 120mg Randomized Withdrawal Phase (RWD) Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
PART A OLT Phase (Day 1 to Day 21) Adverse Event	1	0	0	0
PART B OLT Phase (Day 1 to Day 42) Adverse Event	0	6	0	0

Baseline Characteristics

A Clinical Trial of PRAX-944 in Participants With Essential Tremor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: PRAX-944 20mg to 40mg OLT n=7 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 20mg to 120mg OLT n=17 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks	Total n=24 Participants Total of all reporting groups
Age, Continuous	67.7 years STANDARD_DEVIATION 6.60 • n=5 Participants	59.3 years STANDARD_DEVIATION 13.81 • n=7 Participants	61.8 years STANDARD_DEVIATION 12.62 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	14 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	17 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	6 Participants n=5 Participants	16 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Aborigines	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0), Days 7 and 14

Population: Full Analysis Set (FAS): all participants who took at least 1 dose of study drug and had a valid baseline TETRAS assessment and at least 1 valid post-baseline TETRAS assessment. Only those participants with data available at indicated timepoints have been presented.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=6 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Change from baseline to Day 7	-1.427 Scores on a scale Interval -4.4375 to 1.5845	—	—
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Change from baseline to Day 14	-2.912 Scores on a scale Interval -4.2779 to -1.5466	—	—

PRIMARY outcome

Timeframe: Up to Day 70

Population: Safety Analysis Set included all participants who received at least 1 dose of study drug.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Incidence and Severity of Adverse Events have been reported.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=17 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD n=6 Participants Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD n=5 Participants Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation Mild AE	13 participants	1 participants	1 participants
Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation Any AE	15 participants	1 participants	1 participants
Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation Related AE	12 participants	0 participants	1 participants
Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation AE Leading to Treatment Discontinuation	6 participants	0 participants	0 participants
Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation Moderate AE	7 participants	1 participants	0 participants
Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation Severe AE	0 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: Up to Day 70

Population: Safety Analysis Set

Vital signs parameters included body temperature, pulse rate, respiratory rate, blood pressure (systolic and diastolic), clinical laboratory measures (chemistry, hematology, urinalysis, and coagulation), electrocardiogram parameters (heart rate, PR, QRS, QT, and corrected QT intervals). Any change in vital sign abnormalities that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported as an unsolicited adverse event (AE). Any clinically significant abnormality associated with underlying disease does not require reporting as an (S)AE unless judged by the investigator to be more severe than expected for the participant's condition.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=17 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD n=6 Participants Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD n=5 Participants Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part B: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Up to Day 70

Population: FAS population

The C-SSRS is described as a scale developed at Columbia University that has 2-6 questions each in categories of Suicidal Ideation, Intensity of Ideation, Suicidal Behavior, and Actual Attempts. Four constructs were measured. Severity of Suicidal ideation is rated on a 5-point ordinal scale. Intensity of ideation is comprised of 5 items (frequency, duration, controllability, deterrents, and reason for ideation), each rated on a 5-point ordinal scale. Suicidal behavior is rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. Lethality, assesses actual attempts; actual lethality is rated on a 6-point ordinal scale, and if actual lethality is 0, potential lethality of attempts is rated on a 3-point ordinal scale.The higher the C-SSRS score, the higher the suicide risk (ie. worse outcome).

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=17 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD n=6 Participants Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD n=5 Participants Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part B: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0), Days 7 and 14

Population: FAS population. Only those participants with data available at indicated timepoints have been presented.

The TETRAS is an essential tremor and activities of daily living rating scale. The full scale has 2 sections, the Performance subscale (PS) and the ADL subscale. The PS consists of 9 items covering different body regions. These 9 items are rated on a 5-point scale (ranging from 0 to 4). One item, Item 4, consists of ratings for 3 tasks rated separately for upper limbs on both sides of the body for a total of 6 ratings. The total score of the 9 items (14 ratings) ranges from 0 to 70 with higher scores indicating greater tremor severity. The total score and individual item ratings will be evaluated as outcomes in this trial. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=6 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Change from baseline to Day 7	-1.990 scores on a scale Interval -7.5467 to 3.5672	—	—
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Change from baseline to Day 14	-5.163 scores on a scale Interval -11.1371 to 0.8108	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Days 7 and 14

Population: FAS Population. Only those participants with data available at indicated timepoints have been presented.

Accelerometer was used to evaluate record coordinates and accelerations in the 3D space over time. The 3 maneuvers in the upper limb item will be completed for both arms, first for the right arm and then for the left. Each upper limb sub-item is scored on a scale from 0 to 4 including to 0.1 increments. The accelerometer upper limb total score, ranges from 0 to 24. A decrease in score is indicative of improvement. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=3 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry Change from baseline to Day 7	-1.100 scores on a scale Interval -3.3733 to 1.1733	—	—
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry Change from baseline to Day 14	-1.300 scores on a scale Interval -3.5733 to 0.9733	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Days 7 and 14

Population: FAS population. Only those participants with data available at indicated timepoints have been presented.

The TETRAS ADL subscale is a 12-item assessment of typical daily activities that are impacted by tremor. Activities are assessed in the following functional domains: speaking, feeding, drinking, personal hygiene, dressing, writing, and social activity. The impact to each function is rated on a 5-point Likert scale from 0 to 4. The ADL subscale score is calculated as the sum of all 12 items and ranges from 0 to 48 with higher scores reflecting higher impact. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=6 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item 6 Archimedes Spiral (Right) Change from baseline to Day 7	-0.091 scores on a scale Interval -0.5713 to 0.389	—	—
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item 6 Archimedes Spiral (Left) Change from baseline to Day 7	-0.213 scores on a scale Interval -1.2762 to 0.8501	—	—
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item 7 Handwriting Change from baseline to Day 7	-0.012 scores on a scale Interval -0.7215 to 0.6975	—	—
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item 7 Handwriting Change from baseline to Day 14	-0.348 scores on a scale Interval -1.0966 to 0.4013	—	—
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item 6 Archimedes Spiral (Right) Change from baseline to Day 14	-0.346 scores on a scale Interval -0.9765 to 0.2836	—	—
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item 6 Archimedes Spiral (Left) Change from baseline to Day 14	-0.468 scores on a scale Interval -1.3845 to 0.4487	—	—

SECONDARY outcome

Timeframe: Up to Day 21

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=7 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation Severe AE	0 participants	—	—
Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation Any AE	6 participants	—	—
Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation Related AE	4 participants	—	—
Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation AE Leading to Treatment Discontinuation	1 participants	—	—
Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation Mild AE	6 participants	—	—
Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation Moderate AE	1 participants	—	—

SECONDARY outcome

Timeframe: Up to Day 21

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=7 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters	0 Participants	—	—

SECONDARY outcome

Timeframe: Up to Day 21

Population: Safety Analysis Set

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=7 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part A: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)	0 Participants	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0) and Day 42

Population: FAS Population. Only those participants with data available at indicated timepoints have been presented.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=11 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase	-2.090 scores on a scale Interval -3.8223 to -0.3585	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Days 7 and 21

Population: FAS. Only those participants with data available at indicated timepoints have been presented.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=12 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase Change from baseline to Day 7	-0.967 scores on a scale Interval -2.1795 to 0.2447	—	—
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase Change from baseline to Day 21	-1.143 scores on a scale Interval -2.1269 to -0.1598	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0) and Days 7, 21 and 42

Population: FAS population. Only those participants with data available at indicated timepoints have been presented.

TETRAS Performance Subscale was used to assess essential tremor as scored by the independent video raters. The performance subscale consists of 9 items, i.e. item 1 (head), item 2 (face), item 3 (voice), each of the 6 sub-items for item 4 (upper limb), the maximum of the 4 sub-items for item 5 (lower limb), 2 sub-items (right and left side) for item 6 (Archimedes spirals), item 7 (handwriting), 2 sub-items (right and left side) for item 8 (dot approximation), and item 9 (standing) for a total score ranging from 0 to 64 from 16 sub-items. Each item is rated on a scale of 0 to 4, including 0.5 increments. A lower score is indicative of improvement. The total score has been presented. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=12 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale During OLT Phase Change from baseline to Day 21	-1.449 scores on a scale Interval -3.7708 to 0.8734	—	—
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale During OLT Phase Change from baseline to Day 7	-1.253 scores on a scale Interval -3.8185 to 1.3133	—	—
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale During OLT Phase Change from baseline to Day 42	-2.771 scores on a scale Interval -6.2554 to 0.7127	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), and Days 7, 21 and 42

Population: FAS population. Only those participants with data available at indicated timepoints have been presented.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=11 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry During OLT Phase Change from baseline to Day 7	-1.235 scores on a scale Interval -2.0318 to -0.4376	—	—
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry During OLT Phase Change from baseline to Day 21	-1.835 scores on a scale Interval -2.8523 to -0.8179	—	—
Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry During OLT Phase Change from baseline to Day 42	-1.766 scores on a scale Interval -2.9106 to -0.6223	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Days 7, 21 and 42

Population: FAS Population. Only those participants with data available at indicated timepoints have been presented.

TETRAS Performance Subscale was used to assess essential tremor as scored by the independent video raters. The performance subscale consists of 9 items, i.e. item 1 (head), item 2 (face), item 3 (voice), each of the 6 sub-items for item 4 (upper limb), the maximum of the 4 sub-items for item 5 (lower limb), 2 sub-items (right and left side) for item 6 (Archimedes spirals), item 7 (handwriting), 2 sub-items (right and left side) for item 8 (dot approximation), and item 9 (standing) for a total score ranging from 0 to 64 from 16 sub-items. Each item is rated on a scale of 0 to 4, including 0.5 increments. A lower score is indicative of improvement. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=12 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item#6 Archimedes spirals (right) Change from baseline to Day 7	0.006 scores on a scale Interval -0.4387 to 0.45	—	—
Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item#6 Archimedes spirals (left) Change from baseline to Day 7	0.221 scores on a scale Interval -0.1329 to 0.5739	—	—
Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item#7 Handwriting Change from baseline to Day 7	-0.019 scores on a scale Interval -0.6477 to 0.6087	—	—
Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item#6 Archimedes spirals (right) Change from baseline to Day 21	-0.240 scores on a scale Interval -0.5006 to 0.0202	—	—
Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item#6 Archimedes spirals (left) Change from baseline to Day 21	-0.012 scores on a scale Interval -0.2547 to 0.2316	—	—
Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item#7 Handwriting Change from baseline to Day 21	0.107 scores on a scale Interval -0.3613 to 0.5745	—	—
Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item#6 Archimedes spirals (right) Change from baseline to Day 42	-0.239 scores on a scale Interval -0.6711 to 0.193	—	—
Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item#6 Archimedes spirals (left) Change from baseline to Day 42	-0.072 scores on a scale Interval -0.4488 to 0.3044	—	—
Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) Item#7 Handwriting Change from baseline to Day 42	-0.054 scores on a scale Interval -0.6984 to 0.5911	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Days 7, 21 and 42

Population: FAS population. Only those participants with data available at indicated timepoints have been presented.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=12 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part B: Change From Baseline in TETRAS Activities of Daily Living (ADL) Score Change from baseline to Day 7	-1.986 scores on a scale Interval -4.8142 to 0.8417	—	—
Part B: Change From Baseline in TETRAS Activities of Daily Living (ADL) Score Change from baseline to Day 21	-3.475 scores on a scale Interval -7.026 to 0.0756	—	—
Part B: Change From Baseline in TETRAS Activities of Daily Living (ADL) Score Change from baseline to Day 42	-8.207 scores on a scale Interval -12.5655 to -3.8481	—	—

SECONDARY outcome

Timeframe: Baseline (Day 0), Days 7, 21 and 42

Population: FAS population. Only those participants with data available at indicated timepoints have been presented.

Quality of Life in Essential Tremor Questionnaire (QUEST) is a patient-reported ET-specific 30-item, specific quality of life scale. Items contribute to five dimensions. Physical/ADL (9 items ), Psychosocial (9 items), Communication (3 items), Hobbies/Leisure (3 items), and Work/Finances (6 items). The QUEST total and subscale scores are calculated as the sum of all applicable items divided by the number of applicable items times 100. Higher score indicates greater dissatisfaction with that domain of QOL. Maximal score 100: worse quality of life. Minimal Score 0: best quality of life. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.

Outcome measures

Outcome measures
Measure	Part A: PRAX-944 20mg to 40mg OLT n=10 Participants Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 120mg RWD Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
Part B: Change From Baseline in Quality of Life in Essential Tremor Questionnaire (QUEST) Total Scores. Change from baseline to Day 7	-0.561 scores on a scale Interval -7.7823 to 6.6611	—	—
Part B: Change From Baseline in Quality of Life in Essential Tremor Questionnaire (QUEST) Total Scores. Change from baseline to Day 21	-5.933 scores on a scale Interval -12.1961 to 0.331	—	—
Part B: Change From Baseline in Quality of Life in Essential Tremor Questionnaire (QUEST) Total Scores. Change from baseline to Day 42	-8.203 scores on a scale Interval -17.9048 to 1.4991	—	—

Adverse Events

Part A: PRAX-944 20mg to 40mg Open-Label Titration (OLT)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part B: PRAX-944 20mg to 120mg OLT

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Part B: PRAX-944 120mg Randomized Withdrawal Phase (RWD)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part B: Placebo RWD

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: PRAX-944 20mg to 40mg Open-Label Titration (OLT) n=7 participants at risk Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days).	Part B: PRAX-944 20mg to 120mg OLT n=17 participants at risk Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks.	Part B: PRAX-944 120mg Randomized Withdrawal Phase (RWD) n=6 participants at risk Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days.	Part B: Placebo RWD n=5 participants at risk Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days.
General disorders Cyst	0.00% 0/7 • Adverse Events (AEs) were collected up to Day 70 (up to Day 21 for Part A and up to Day 70 for Part B) All Adverse Events were collected from the time the participant provided consent to participate in the study until the end of the study (last study visit) for the participant.	5.9% 1/17 • Adverse Events (AEs) were collected up to Day 70 (up to Day 21 for Part A and up to Day 70 for Part B) All Adverse Events were collected from the time the participant provided consent to participate in the study until the end of the study (last study visit) for the participant.	0.00% 0/6 • Adverse Events (AEs) were collected up to Day 70 (up to Day 21 for Part A and up to Day 70 for Part B) All Adverse Events were collected from the time the participant provided consent to participate in the study until the end of the study (last study visit) for the participant.	0.00% 0/5 • Adverse Events (AEs) were collected up to Day 70 (up to Day 21 for Part A and up to Day 70 for Part B) All Adverse Events were collected from the time the participant provided consent to participate in the study until the end of the study (last study visit) for the participant.

Other adverse events

Additional Information

Charmaine Manilay

Praxis Precision Medicines

Phone: 2243996121

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place